Elevated miR‐124‐3p in the aging colon disrupts mucus barrier and increases susceptibility to colitis by targeting T‐synthase,Aging Cell

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Elevated miR‐124‐3p in the aging colon disrupts mucus barrier and increases susceptibility to colitis by targeting T‐synthase
Aging Cell ( IF 8.0 ) Pub Date : 2020-10-11 , DOI: 10.1111/acel.13252
Li Huang ₁ , Ting-Yi Sun _{1,

2,

3} , Liang-Jun Hu ₁ , Shi-Long Hu ₁ , Hai-Mei Sun _{1,

2,

3} , Fu-Qian Zhao ₁ , Bo Wu _{1,

2,

3} , Shu Yang _{1,

2,

3} , Feng-Qing Ji _{1,

2,

3} , De-Shan Zhou _{1,

2,

3}

Affiliation

The risk of colitis and colorectal cancer increases markedly throughout adult life, endangering the health and lives of elderly individuals. Previous studies have proposed that bacterial translocation and infection are the main risk factors for these diseases. Therefore, in the present study, we aimed to identify the underlying mechanism by focusing on the mucus barrier function and mucin‐type O‐glycosylation. We evaluated alterations in the colon mucus layer in 2‐, 16‐, and 24‐month‐old mice and aged humans. Aged colons showed defective intestinal mucosal barrier and changed mucus properties. The miR‐124‐3p expression level was significantly increased in the aged distal colonic mucosa, which was accompanied by an increase in pathogens and bacterial translocation. Meanwhile, T‐synthase, the rate‐limiting enzyme in O‐glycosylation, displayed an age‐related decline in protein expression. Further experiments indicated that miR‐124‐3p modulated O‐glycosylation by directly targeting T‐synthase. Moreover, young mice overexpressing miR‐124‐3p exhibited abnormal glycosylation, early‐onset, and more severe colitis. These data suggest that miR‐124‐3p predisposes to senile colitis by reducing T‐synthase, and the miR‐124‐3p/T‐synthase/O‐glycans axis plays an essential role in maintaining the physiochemical properties of colonic mucus and intestinal homeostasis.

中文翻译：

衰老结肠中升高的 miR-124-3p 通过靶向 T-合酶破坏粘液屏障并增加对结肠炎的易感性

结肠炎和结直肠癌的风险在整个成年期显着增加，危及老年人的健康和生命。以前的研究提出细菌易位和感染是这些疾病的主要危险因素。因此，在本研究中，我们旨在通过关注粘液屏障功能和粘蛋白型O-糖基化来确定潜在机制。我们评估了 2、16 和 24 个月大的小鼠和老年人的结肠粘液层的变化。老化的结肠显示有缺陷的肠粘膜屏障并改变了粘液特性。该的miR - 124 - 3P在衰老的远端结肠黏膜中表达水平显着增加，伴随着病原体和细菌易位的增加。同时，O-糖基化的限速酶T-合酶显示出与年龄相关的蛋白质表达下降。进一步的实验表明，的miR - 124 - 3P调制ö通过直接靶向T-合酶-glycosylation。此外，年轻的老鼠过度表达的miR - 124 - 3P表现异常的糖基化，早发，更严重的结肠炎。这些数据表明miR ‐ 124 ‐ 3p易患老年性结肠炎通过降低T-合酶，和的miR - 124 - 3P / T-合酶/ ö -glycans轴在维持结肠粘液和肠稳态的生理化学性质的重要作用。

更新日期：2020-11-23

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